A study of the etiology of alcoholism would benefit from utilizing an animal model. On the strong presumption that the human addiction rests on alcohol's pharmacodynamic rather than its oro-sensory or caloric effects, our objective is to breed rat strains disparate in their reactivity towards alcohol. Using sub-hypnotic doses of alcohol (1.5 g/kg), two strains have been selectively outbred for six generations: the "most affected" strain has a mean reduction of 91% in motor activity while the "least affected" strain suffers only a 38% reduction; there remains considerable variance in activity. We propose to continue this process for another 5 to 7 generations and then to fix the phenotype by brother-sister matings. At the same time, we propose to measure the relation, if any, between responsivity towards alcohol and 1) alcohol self-selection; 2) specificity of the CNS effect (employing other depressant agents); 3) liability of addiction to alcohol and other addictive agents; 4) ease of induction of sustained voluntary consumption of intoxicating amounts of alcohol; 5) metabolic differences in the metabolism of alcohol and acetaldehyde; and 6) endogenous and alcohol-induced neurochemical differences.